1. DNA-Protein Interaction The first aim is to better understand the molecular basis of DNA-protein recognition and the regulation of gene expression. Studies will be continued of the cro repressor protein from bacteriophage lambda, for which the three-dimensional structure has been determined. Mutant cro proteins with unexpected changes in DNA binding and/or protein stabilities will also be studied crystallographically. Attempts will be continued to determine the structure of cro complexed with appropriate DNA fragments. Attempts to determine the structures of the MerR metalloregulatory protein and other DNA binding proteins, as well as complexes of these proteins with DNA will also be pursued. 2. Protein Folding, Function, and Evolution The second goal is to better understand the factors that determine the structure, stability, dynamics, folding and activity of proteins. Ongoing genetic, structural and thermodynamic studies of mutant phage lysozymes, as well as comparative studies of goose lysozyme, phage P22 lysozyme, and other proteins, provide a very favorable experimental framework within which to address these problem areas.